The clinical outcomes, response to treatment and epidemic dynamics of HIV-1 in the UK

Lead Research Organisation: University College London
Department Name: Infection and Population Health

Abstract

The characteristics of individuals with HIV in the UK are changing with a much greater number of those living with HIV being women. Treatments for HIV are now very effective and many people infected with the virus are able to live almost normal lives. As a result, not only is the HIV-infected population growing older, but many of the women are starting their own families. Even if these women do not yet require treatment for their own health, they may be treated for short periods of time to prevent their babies from becoming infected with HIV. This treatment is very effective and only a very small number of HIV-infected babies are now born in the UK each year. Treatment may be further complicated among individuals who are also infected with hepatitis C or B virus ? these individuals may require earlier treatment and/or different drug combinations than those who are only infected with HIV.

Despite the benefits of treatment, the drugs may still occasionally fail in an individual. This may be because the individual develops side effects to the drugs, or that they find it difficult to take their drugs at exactly the same time every day. When treatments fail, the virus may become resistant to the drugs that the patient is receiving, and this may have knock-on effects for their future treatment choices. Consequently, doctors have started to change the way in which they treat HIV-infected people; for example, treatment may be started earlier and different drug combinations may be used which aim to reduce the risk of side effects, whilst minimising the risk that a patient?s virus will become resistant. In order to plan the future care for these individuals, we need to monitor the use of treatment in HIV-infected persons, and the outcomes of those who receive it.

Two large ongoing studies in the UK, the UK CHIC Study and the UK HDRD, have been monitoring outcomes (e.g. use of treatment, AIDS events, deaths, development of resistance) in HIV-infected persons since 2001. This proposal requests funding to continue to expand and monitor these cohorts so that the information they provide remains timely and accurate. In addition to monitoring outcomes, we also plan to investigate whether treatment received during pregnancy has any long-term effects on the mother?s health, and whether infection with hepatitis B or C accelerates the progression of HIV disease, or reduces the benefits of treatments.

Technical Summary

The use of highly active antiretroviral therapy (HAART) has had a major impact on the health of HIV-infected individuals in the developed world and, as a result, life expectations of those infected with HIV have started to approach those seen in the general population. However, treatment paradigms are changing and over the next five years we expect to see changes in the drugs/drug combinations used, the order in which they are sequenced and the CD4 count at which treatment is started. However, the development and transmission of resistant HIV remains a threat to successful treatment. Furthermore, those living with are now older, a greater proportion are women (many of whom are becoming pregnant and receiving treatment to prevent transmission of HIV to their baby) and many are co-infected with viral hepatitis; these factors may complicate the management of those with HIV. In order to plan the need for health-care services and to understand the need for new antiretroviral drugs in HIV-infected persons, it is important to continue to monitor the outcomes of treatment in this population, including the incidence and patterns of drug resistance, and to determine the degree to which the efficacy of future drugs is likely to be compromised by resistance development.

The UK Collaborative HIV Cohort (CHIC) Study and UK HIV Drug Resistance Database (UK HDRD) were initiated in 2001 to monitor the uptake and response to HAART among individuals with HIV in the UK, and the development of resistance in these individuals. The main objective of this programme grant application is to continue to follow these two large cohorts (with expansion where possible so that they continue to follow a large and geographically representative group of patients) with the aim of providing timely information on the changing trends over time. In addition, several other questions have arisen which must now be addressed, relating particularly to the use of treatment during pregnancy and the impact of long-term co-infection with hepatitis viruses. Thus, we propose to develop five complementary themes of research (ongoing monitoring of outcomes; understanding the transmission and persistence of resistance; understanding the molecular epidemiology of the UK epidemic; describing the impact on women of antiretroviral treatment received during pregnancy; and describing the impact of co-infection with hepatitis B/C on HIV outcomes). Each theme will include a series of co-ordinated projects covering questions across the broad scientific area.

Publications

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Antiretroviral Therapy Cohort Collaboration (ART-CC) (2016) Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada: collaborative cohort analysis. in AIDS (London, England)

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Booth JW (2016) Clinical characteristics and outcomes of HIV-associated immune complex kidney disease. in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

 
Guideline Title BHIVA Monitoring Guidelines
Description BHIVA Monitoring Guidelines
Geographic Reach Europe 
Policy Influence Type Citation in clinical guidelines
 
Guideline Title BHIVA Treatment Guidelines
Description BHIVA treatment guidelines
Geographic Reach Europe 
Policy Influence Type Citation in clinical guidelines
 
Guideline Title Various guidelines for monitoring and treatment of patients with HIV
Description Citation in treatment guidelines
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
 
Title UK CHIC database 
Description The UK CHIC database is expanded on a yearly basis through this grant 
Type Of Material Biological samples 
Year Produced 2010 
Provided To Others? Yes  
Impact Ongoing research collaborations with external organisations 
 
Title UK HDRD Data Dictionary 
Description Data dictionary for UK HIV Drug Resistance Database 
Type Of Material Improvements to research infrastructure 
Year Produced 2012 
Provided To Others? Yes  
Impact Simplification of data submission process and increased possibilities for collaboration 
 
Description HIV-CAUSAL (Harvard University plus others) 
Organisation Harvard University
Country United States 
Sector Academic/University 
PI Contribution Intellectual input into study design and analysis; provision of datasets; writing manuscripts
Impact Several publications in high impact journals, all are listed in appropriate section
Start Year 2009
 
Description HCV Research UK Launch meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Gave talk to investigators of new HCV cohort study about experiences in similar studies in HIV so that we could cross-fertilise ideas

None as yet
Year(s) Of Engagement Activity 2013
 
Description UK HIV Community Advisory Board 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact Members of the study team provided information about the UK CHIC and UK HDRD studies to 30 representatives from the UK HIV Advisory Group, and answered questions about the studies afterwards.

Discussions from this meeting led to several agreements for new analyses at the request of the HIV patient community.
Year(s) Of Engagement Activity 2010
 
Description WHO HIV ResNet HIV Drug Resistance Surveillance Meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Provided statistical input on a debate on the use of the finite population correction in survey research and sampling strategies for surveys to estimate the prevalence of transmitted HIV drug resistance

None as yet.
Year(s) Of Engagement Activity 2013